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제109회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Synthesis and preliminary evaluation of activity of potential inhibitors of Nitric Oxide Synthase (NOS)

2012년 2월 23일 14시 09분 34초
MEDI.P-1024 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
4월 25일 (수요일) 18:00~21:00
저자 및
Ashrafuzzaman MD, 정찬성1
과학기술연합대학원대학교 Green Chem. & Env.BT, Korea
1한국과학기술연구원 케모인포매틱스연구단, Korea
NOSs (Nitric Oxide Synthases) are the only enzymes known to simultaneously require five bound cofactors/prosthetic groups; FAD, FMN, Haem, tetrahydrobiopterin (BH4) and Ca2+-calmodulin (CaM). NO (Nitric Oxide) is an important cellular signaling molecule, having a vital role in many diverse biological processes. NOS catalyzes the synthesis of Nitric Oxide (NO) from the terminal nitrogen atom of L-arginine (L-Arg) in the presence of NADPH and dioxygen (O2). In mammals, three distinct genes encode NOS isozymes: neuronal (nNOS or NOS1), cytokine-inducible (iNOS or NOS2), and endothelial (eNOS or NOS3). NOSs are usually existed as dimer in their active form, required BH4((6R))-5,6,7,8-tetrahydrobiopterin) by cofactor. Recently, Bacterial NOS (bNOS) has been shown to protect bacteria against oxidative stress, diverse antibiotics, and host immune response. Although NO mediates several physiological functions, its overproduction has been reported in a number of clinical disorders, including neurodegenerative disorders (Parkinson’s disease, Alzheimer’s disease). Our designed pyrimidine derivatives were synthesized by Vilsmeier-Haack reaction and cyclization. Block the BH4 binding site using our designed compounds induce instabilization of NOS, as a result, overproduction of NO is expected to be reduced, which could therefore be a useful intervention in the treatment of various diseases.